The majority of B lymphocytes which populate the spleens of adult mice bear receptor immunoglobulin of two classes, IgM and IgD. Many of these cells may have additional receptors for LPS and/or T cell derived factors. In recent studies, we have demonstrated that receptor IgM and IgD have distinctly different functions. IgD confers upon the B cell, increased resistance to tolerance induction. Antibody mediated blocking studies indicate that receptor Ig of both classes must interact with antigen to achieve immune activation with the thymus dependent antigen TNP-SRBC, while antigen need only interact with receptor IgM to achieve activation with TNP-Brucella abortus, a thymus independent antigen. Further incisive studies of the dynamics of cell membrane receptors and related events during and after antigen interaction are essential for our understanding of immune activation, and this induction and maintenance of self tolerance in B cells. In general, objectives of this proposal include: (1) To catalog B cell subsets on the basis of their responsiveness to hapten on various carriers, tolerance susceptibility, and receptor distribution. (2) To study, using isolated antigen specific cells, the fate of antigen, and receptors for antigen, LPS and T cell derived helper factors during and following interaction of cells with tolerogen or immunogen. (3) And finally, to study the ability of anti-heavy chain reagents, T helper factors, mitogens and pharmacologic agents to modulate activation and tolerance and concommitant cellular events. These studies should provide insight into the functions of B-cell surface markers in immunologic phenomena.